CLINICAL GUIDELINES 1

American Gastroenterological Association-American

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College of Gastroenterology Clinical Practice Guideline:

Pharmacological Management of Chronic
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Idiopathic Constipation
Lin Chang, MD, AGAF, FACG1,*, William D. Chey, MD, FACG2,*, Aamer Imdad, MBBS, MPH3,*,
Christopher V. Almario, MD, MSHPM, FACG4, Adil E. Bharucha, MD5, Susan Diem, MD, MPH6,7, Katarina B. Greer, MD, MS Epi8,9,
Brian Hanson, MD6,10, Lucinda A. Harris, MD, FACG11, Cynthia Ko, MD12, M. Hassan Murad, MD13, Amit Patel, MD, FACG14,
Eric D. Shah, MD, MBA, FACG2,15, Anthony J. Lembo, MD, FACG16,† and Shahnaz Sultan, MD, MHSc, FACG6,17,†

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in
quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological
Association and the American College of Gastroenterology, aims to inform clinicians and patients by
providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults.
METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a
multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic
laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate,
senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride).
The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment,
Development, and Evaluation framework to assess the certainty of evidence for each intervention. The
Evidence to Decision framework was used to develop clinical recommendations based on the balance between
the desirable and undesirable effects, patient values, costs, and health equity considerations.

RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based
on available evidence, the panel made strong recommendations for the use of polyethylene glycol,
sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional
recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone.
DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription
pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for
approaching the management of CIC; clinical providers should engage in shared decision making based on
patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are
highlighted to help guide future research opportunities and enhance the care of patients with chronic
constipation.

1
Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; 2Division of Gastroenterology
& Hepatology, Michigan Medicine, Ann Arbor, Michigan, USA; 3Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, SUNY Upstate
Medical University, Syracuse, New York, USA; 4Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los
Angeles, California, USA; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA; 6Minneapolis
VA Healthcare System, Minneapolis, Minnesota, USA; 7University of Minnesota School of Medicine, Minneapolis, Minnesota, USA; 8Cleveland VA Healthcare
System, Cleveland, Ohio, USA; 9Case Western Reserve University, Cleveland, Ohio, USA; 10Department of Medicine, University of Minnesota, Minneapolis,
Minnesota, USA; 11Division of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, Arizona, USA; 12Division of Gastroenterology & Hepatology, University of
Washington, Washington, DC, USA; 13Mayo Clinic, Rochester, Minnesota, USA; 14Division of Gastroenterology, Duke University School of Medicine and the Durham
Veterans Affairs Medical Center, Durham, North Carolina, USA; 15Division of Gastroenterology & Hepatology, Department of Medicine, DartMouth Health, Lebanon,
New Hampshire, USA; 16Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute; Cleveland Clinic, Cleveland, Ohio, USA;
17
University of Minnesota, Minneapolis, Minnesota, USA. Correspondence: Lin Chang, MD, FACG. E-mail: linchang@mednet.ucla.edu.
*Lin Chang, William D. Chey, and Aamer Imdad contributed equally to this work as co-first authors.
†Anthony J. Lembo and Shahnaz Sultan contributed equally to this work as co-senior authors.
This article is being published jointly in The American Journal of Gastroenterology and Gastroenterology. The article is identical except for minor stylistic and spelling differences
in keeping with each journal’s style. Citations from either of the journals can be used when citing this article.
Received January 13, 2023; accepted February 27, 2023

© 2023 by The American College of Gastroenterology and the American Gastroenterological Association The American Journal of GASTROENTEROLOGY
 2 Chang et al
KEYWORDS: fiber; polyethylene glycol; magnesium oxide; lactulose; docusate; bisacodyl; senna; sodium picosulfate; lubiprostone;
linaclotide; plecanatide; prucalopride
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/C894
Am J Gastroenterol 2023;00:1–19. https://doi.org/10.14309/ajg.0000000000002227; published online May 19, 2023
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EXECUTIVE SUMMARY
Chronic idiopathic constipation (CIC) is a common clinical di-
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agnosis that affects approximately 8%–12% of the US population
(1). Nonpharmacological therapies often represent the initial
steps in management and may include dietary recommendations
(such as increased fluid intake and increased dietary fiber) and
behavioral changes (such as exercise). Pharmacological treatment
may include the use of over-the-counter (OTC) or prescription
medications, such as polyethylene glycol (PEG), secretagogues, or
prokinetic agents (2). This joint evidence-based guideline from
the American Gastroenterological Association (AGA) and the
American College of Gastroenterology (ACG) aims to provide
recommendations for the pharmacological management of CIC
in adults.
HOW TO READ THESE GUIDELINES
Table 1 provides an overview of each guideline recommendation
along with the associated certainty of evidence and the strength of
recommendation. Additional information about the background,
methods, evidence reviews, and detailed justifications for each
recommendation is provided after Table 1 for readers wishing to
read the full guideline. Corresponding forest plots for each in-
tervention and evidence profiles which provide a synthesis of the
evidence as well as Evidence to Decision (EtD) framework tables
that summarize the panel’s detailed judgments supporting each
recommendation are provided in the Supplementary Document
(see Supplementary Digital Content 1, http://links.lww.com/
AJG/C894). Each recommendation is accompanied by clinical
practice considerations (based on the collective experience of the
panel members) that are meant to help guideline users implement
the recommendations. The term “recommend” was used to in-
dicate strong recommendations, and the term “suggest” was used
to indicate conditional recommendations. The interpretation of
certainty of evidence and implications of strong and conditional
recommendations for healthcare providers, patients, and poli-
cymakers are presented in Tables 2 and 3, respectively. For all the
recommendations, the alternative approach was management of
CIC without the intervention.
INTRODUCTION
Description of the health problem
CIC is a common clinical diagnosis that affects approximately
8%–12% of the US population (1). CIC is a lower gastrointestinal
(GI) tract disorder of gut-brain interaction and can be associated
with symptoms such as infrequent and incomplete defecation in
the absence of mucosal or structural abnormalities (2,3). The
medical costs related to the management of constipation are es-
timated to be between approximately $2,000 and $7,500 US
dollars per patient per year, and the effects on quality of life can be
similar to those associated with conditions such as chronic ob-
structive pulmonary disease, diabetes, and depression (4,5).
Nonpharmacological interventions often represent the initial step
The American Journal of GASTROENTEROLOGY
in management and may include dietary (such as increased fluid
intake and increased dietary fiber) and behavioral changes (such
as exercise). Pharmacological treatment may include the use of
PEG, secretagogues, and prokinetic agents (2,6,7). Overall, a
significant proportion of patients with CIC are not satisfied with
their treatment and may use multiple OTC medications, followed
by prescription medications before they have improvement in
their symptoms (8–10).
Objective of the review and guideline
The AGA and ACG jointly developed this systematic review and
clinical guideline to provide evidence-based recommendations
for the pharmacological management of CIC in adults.
Target audience
The target audience for these guidelines includes primary care,
internal medicine, family medicine, and gastroenterology
healthcare providers; patients; and policymakers. The recom-
mendations in this document are not intended to be used as the
standard of care. Instead, they can be used to guide the man-
agement of adult patients with CIC. Although no single recom-
mendation can encompass every individual circumstance and
context, it can be used to address the benefits and harms of
treatments and support the processes of shared decision making
so that patients are treated based on their values and preferences.
METHODS
Overview
This document represents the official recommendations of the
AGA and ACG. These recommendations were developed using
the Grading of Recommendations Assessment, Development,
and Evaluation (GRADE) approach.
Organization and panel composition
The guideline panel members from the AGA and ACG were
selected based on their clinical and methodological expertise.
Each member underwent a vetting process that required dis-
closing all conflicts of interest. The panel included 3 guideline
committee members specializing in general gastroenterology,
motility, and primary care. Panel members comprising the evi-
dence review team (divided into 3 subcommittees) included
gastroenterologists with expertise in CIC, 1 senior methodologist,
and 3 junior methodologists. All included interventions were
divided among the 3 subcommittees (see Supplementary Table 1,
Supplementary Digital Content 1, http://links.lww.com/AJG/
C894). The senior methodologist supervised the evidence syn-
thesis for all the interventions across the 3 subcommittees.
Members of the guideline committee helped review all the syn-
thesized evidence, contributed to discussion, and helped develop
the clinical decision support tool. A librarian assisted with de-
signing and executing the relevant literature searches. An exec-
utive committee of members of the AGA and ACG were
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Table 1. Summary of recommendations and implementation
considerations
Recommendations
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Fiber
Recommendation 1: In adults with CIC,
the panel suggests the use of fiber
supplementation over management
without fiber supplements
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Implementation considerations
• Dietary assessment is important to
determine total fiber intake from diet
and supplements
• Fiber supplements can be used as
first-line therapy for CIC, particularly
for individuals with low dietary fiber
intake
• Among the evaluated fiber
supplements, only psyllium
appears to be effective (with very
limited and uncertain data on
bran and inulin)
• Adequate hydration should be
encouraged with the use of fiber
• Flatulence is a commonly
observed side effect with the
use of fiber
Osmotic laxatives
Recommendation 2: In adults with CIC,
the panel recommends the use of PEG
compared with management without
PEG
Implementation considerations
• A trial of fiber supplement can be
considered for mild constipation
before PEG use or in combination with
PEG
• Response to PEG has been shown to
be durable over 6 mo
• Side effects include abdominal
distension, loose stool, flatulence, and
nausea
Recommendation 3: In adults with CIC,
the panel suggests the use of
magnesium oxide over management
without magnesium oxide
Implementation considerations
• The trials were conducted for 4 wk,
although longer term use is probably
appropriate
• The panel suggests starting at a lower
dose, which may be increased if
necessary
• Avoid use in patients with renal
insufficiency due to risk of
hypermagnesemia
© 2023 by The American College of Gastroenterology and the American Gastroenterological Association
Clinical Practice Guidelines 3
Table 1. (continued)
Strength of Certainty of
Strength of Certainty of Recommendations recommendation evidence
recommendation evidence Recommendation 4: In adults with CIC Conditional Very low
who fail or are intolerant to OTC
Conditional Low therapies, the panel suggests
the use of lactulose over
management without
lactulose
Implementation considerations
• Bloating and flatulence are dose-
dependent and common side effects,
which may limit its use in clinical
practice
Stimulant laxatives
Recommendation 5: In adults with CIC, Strong Moderate
the panel recommends the use of
bisacodyl or sodium picosulphate short
term or as rescue therapy over
management without bisacodyl or
sodium picosulphate
Implementation considerations
• Short-term use is defined as daily
use for 4 wk or less. While long-term
use is probably appropriate, data are
needed to better understand tolerance
and side effects
• This is a good option for
Strong Moderate occasional use or rescue
therapy in combination
with other pharmacological
agents for CIC
• The most common side effects are
abdominal pain, cramping and
diarrhea. The panel suggests starting
at a lower dose and increasing the
dose as tolerated
Recommendation 6: In adults Conditional Low
with CIC, the panel suggests the
use of senna over management
without senna
Implementation considerations
Conditional Very low • While the trials were conducted for 4
wk, longer term use is probably
appropriate, but data are needed to
better understand tolerance and side
effects
• The dose evaluated in trials is higher
than commonly used doses in
practice. The panel suggests starting
at lower dose and increase if no
response
• Abdominal pain and cramping
may occur with a higher dose
of senna
Secretagogues
The American Journal of GASTROENTEROLOGY
 4 Chang et al
Table 1. (continued)
Recommendations
Recommendation 7: In adults with CIC
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who do not respond to OTC agents, the
panel suggests the use of lubiprostone
over management without lubiprostone
Implementation considerations
• Can be used as a replacement or as an
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adjunct to OTC agents
• Duration of treatment in trials was 4 wk,
but the drug label does not provide a limit
• Nausea may occur; however, the risk of
nausea is dose-dependent and seems to
be lower when taken with food and water
Recommendation 8: In adults with CIC who
do not respond to OTC agents, the panel
recommends the use of linaclotide over
management without linaclotide
Implementation considerations
• Can be used as a replacement or as an
adjunct to OTC agents
• Duration of treatment in trials was 12 wk
but the drug label does not provide a limit
• May be associated with side effects of
diarrhea leading to discontinuation of
treatment
Recommendation 9: In adults with CIC
who do not respond to OTC agents, the
panel recommends the use of plecanatide
over management without plecanatide
Implementation considerations
• Can be used as a replacement or as an
adjunct to OTC agents
• Duration of treatment in trials was 12 wk,
but the drug label does not provide a limit
• May be associated with side effects of
diarrhea leading to discontinuation of
treatment
5-HT4 agonist
Recommendation 10: In adults with CIC
who do not respond to OTC agents, the
panel recommends the use of prucalopride
over management without prucalopride
Implementation considerations
• Duration of treatment in trials was 4–24 wk
but the drug label does not provide a limit
• Can be used as a replacement or as an
adjunct to OTC agents
• May be associated with side effects of
headache, abdominal pain, nausea,
and diarrhea
The implementation considerations are based on the collective experience of
the panel members, and evidence may not be available for each of the
implementation considerations.
5-HT4, serotonin type 4; CIC, chronic idiopathic constipation; OTC, over-the-
counter; PEG, polyethylene glycol.
The American Journal of GASTROENTEROLOGY
responsible for oversight of this collaborative guideline (S.S.,
W.D.C., L.C., A.L.).
Strength of Certainty of
Management of conflict of interest and guideline funding
recommendation evidence
Panel members disclosed all potential conflicts of interest. Con-
Conditional Low flicts were managed according to AGA and ACG policies, the
National Academy of Medicine, and Guidelines International
Network standards (11–13). Panel members determined to have a
potential conflict of interest with a specific intervention or agent
were allocated to a subcommittee that did not include the specific
intervention(s). Development of this guideline was wholly funded
by the AGA and ACG with no support from the industry.
Scope
The guideline panel and evidence review team formulated clinically
relevant questions on the pharmacological therapies for CIC in
adults. The last position paper by the AGA on CIC included
Strong Moderate guidance on clinical evaluation, diagnostics tests, and medical and
surgical management (6). This document does not specifically
address considerations related to special populations such as those
with malignancy, pregnancy, or opioid-induced constipation.
Formulation of clinical questions and determining outcomes
of interest
PICO format. For each guideline question, the evidence review
team conducted a systematic review. The systematic review was
based on specific Population, Intervention, Comparison, Out-
come (PICO) questions developed by the guidelines committee
and approved by the Boards of both organizations. A protocol
Strong Moderate guided the systematic review process and is registered at the in-
ternational Prospective Register of Systematic Reviews website
(CRD42021254673). In summary, we included individual ran-
domized controlled trials (RCTs). We also considered the trials
with multiple arms and included comparisons where the only
difference between the 2 groups was the intervention of interest. If
a study included multiple treatment arms but only 1 comparison
group, we combined the treatment arms when appropriate so that
the comparison group was not counted twice in the meta-
analysis.
Population. The population of interest was adults (18 years or
older) diagnosed with CIC. We excluded studies where individ-
uals were diagnosed with other similar conditions such as opioid-
induced constipation or constipation due to other medical
Strong Moderate
conditions such as hypothyroidism and celiac disease. We also
excluded studies in patients with irritable bowel syndrome with
constipation (IBS-C) because the pharmacological management
of IBS-C was covered in another recent AGA (14) and ACG
guideline (15).
Intervention. We included the following interventions: fiber:
psyllium, bran, methylcellulose, and inulin; osmotic or surfactant
laxatives: PEG, magnesium oxide (MgO), lactulose, and docusate;
stimulant laxatives: bisacodyl, senna, and sodium picosulfate;
secretagogues: lubiprostone, linaclotide, and plecanatide; and
serotonin type 4 (5-HT4) agonist: prucalopride. We considered
studies that included the above interventions, regardless of the
dose or route of administration. We included studies in which
the intervention duration was at least 4 weeks. We analyzed all the
interventions separately.
Comparison. The comparison group included placebo, no in-
tervention, or standard of care. We excluded studies that
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Table 2. Interpretation of the certainty of effects using the
GRADE framework
Certainty of evidence Definition
High We are very confident that the true effect lies
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close to that of the estimate of the effect.
Moderate We are moderately confident that the true effect
lies close to that of the estimate of the effect. There
is a possibility that it is substantially different.
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Low Our confidence that the true effect lies close to
that of the estimate of the effect is low. The true
effect may be substantially different from the
estimate of the effect.
Very low Our confidence that the true effect lies close to
that of the estimate of the effect is very low. The
true effect is likely substantially different from
the estimate of the effect.
GRADE, Grading of Recommendations Assessment, Development, and Evaluation.
compared different doses or frequencies of the same drug and did
not include a comparison group that did not receive the drug. We
also excluded studies that compared different pharmacological
agents for CIC, and there was no placebo group.
Outcomes. We considered the following outcomes: complete
spontaneous bowel moments (CSBMs) per week; spontaneous
bowel movements (SBMs) per week; responder rate, defined as
CSBM per week of equal or greater than 3 and increased by at least 1
from baseline; diarrhea (adverse event) leading to discontinuation
of treatment; serious adverse events; global relief outcome; quality-
of-life scores (using the Patient Assessment of Constipation-
Quality of Life, or PAC-QOL); and stool form. We considered the
outcomes of CSBMs per week, SBMs per week, and adverse events
leading to discontinuation of medication as the critical outcomes.
Search strategy
A comprehensive search was conducted on the following data-
bases: EMBASE, MEDLINE, Cochrane, Scopus, Web of Science,
ClinicalTrials.gov, Centre for Reviews and Dissemination, and
PubMed. We also reviewed the reference sections of available
systematic reviews (7,8,16,17) and updated the searches if a recent
systematic review was available. The literature was first searched on
May 15, 2021, and the search was updated on November 5, 2022.
The search terms used can be found in Appendix 1 (see Supple-
mentary Digital Content 1, http://links.lww.com/AJG/C894).
Study selection, data collection, and analysis
Searches from all the databases were combined in bibliographic
software (EndNote) (18), and duplicates were removed. Two
reviewers screened the titles and conducted a full-text review of
the eligible studies (using a reference software Covidence), and a
consensus was reached on inclusion (19). Any conflicts were re-
solved with the help of a senior member of the team. Data were
extracted from each study, including study characteristics, such
as year of publication, study site, study population, dose and
frequency of intervention, comparison group, outcomes and
methods for risk-of-bias assessment. Meta-analysis was con-
ducted when more than 1 study contributed data for the same
intervention and outcome. We combined the dichotomous
© 2023 by The American College of Gastroenterology and the American Gastroenterological Association
Clinical Practice Guidelines 5
outcomes to obtain a relative risk (RR) and 95% confidence in-
terval (CI). We used the mean difference (MD) to pool the con-
tinuous outcomes (20). For the meta-analysis, we used the generic
inverse variance method of weighting and applied the random-
effects model. We assessed the statistical heterogeneity by using
the I2 index and x2 statistic. We used funnel plots to assess the
small study effect and publication bias when at least 10 studies
were available in a pooled analysis. We used RevMan (21) soft-
ware for all the statistical analyses. We used the Cochrane Risk of
Bias tool to assess the risk of bias in the included studies (22). This
tool assesses the risk of bias in the following domains: sequence
generation, allocation concealment, blinding, incomplete out-
come data, selective reporting, and other biases (22).
Certainty of the evidence
We used the GRADE approach to assess the certainty of evidence
for the effect of the intervention on each outcome using the
software GradePro (23). The GRADE approach considers factors
such as study design, risk of bias, inconsistency, indirectness,
imprecision, and risk of publication bias to rate the certainty of
evidence as high, moderate, low, or very low (24) (Table 2). The
results of certainty assessment are reported in evidence profiles
available in the Supplementary Document (see Supplementary
Digital Content 1, http://links.lww.com/AJG/C894) for all the
interventions included in this review.
Development of recommendations
The process of translation of evidence into guideline recom-
mendations followed the GRADE EtD framework (25) and was
achieved by discussion during virtual meetings of the guideline
committee. The EtD framework considers the certainty of evi-
dence, balance of benefits and harm, patient values and prefer-
ences, feasibility, acceptability, equity, and resource use (25). All
10 EtD tables are presented in the Supplementary Document (see
Supplementary Digital Content 1, http://links.lww.com/AJG/
C894). Consensus was reached for all the recommendations
among the group. The interpretation of strength of recommen-
dations is summarized in Table 3.
Document review
The guideline underwent expedited internal and external peer
review. The guideline document was revised to address pertinent
comments, but no changes were made to the direction or strength
of recommendations.
Recommendations
The literature search yielded 993 titles, and a total of 726 titles and
abstracts were screened after the duplicates were removed. Of 54
studies reviewed with full text, 28 studies were included in evi-
dence synthesis and 14 studies were excluded (Figure 1). Sup-
plementary Table 2 (see Supplementary Digital Content 1, http://
links.lww.com/AJG/C894) gives the reason for exclusion of
studies. The summary estimates for effect of a specified in-
tervention on each of the prespecified outcome are included as
forest plots and evidence profiles for each PICO question and are
available in the Supplementary Document (see Supplementary
Digital Content 1, http://links.lww.com/AJG/C894).
Table 1 provides a summary of the recommendations pre-
sented in this guideline. More detailed information regarding the
medication indication, dosing, availability, and mechanism of
action is summarized in Table 4.
The American Journal of GASTROENTEROLOGY
 6 Chang et al

Benefits and harms. Based on this 1 small study, bran may lead to
Table 3. Interpretation of a strong and conditional an increase in SBMs per week; however, the CI was wide and
recommendation included a possible null effect (MD 1.30, CI 20.98 to 3.58) (26).
Only 1 adverse event was noted in the treatment group compared
Conditional
with no events in the placebo arm (RR 2.79, CI 0.12–62.48) (26).
Implications Strong recommendation recommendation
There were no data on CSBMs per week, responder rates, di-
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For patients Most individuals in this
situation would want the
recommended course of
action and only a small
proportion would not.
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The majority of individuals in
this situation would want the
suggested course of action,
but many would not.
arrhea, global relief, quality of life, or stool form.
Certainty in evidence of effects. We are very uncertain about the
effects of bran. The overall certainty of evidence for bran is very low
because of concerns about the adequacy of randomization and
allocation concealment as well as very serious imprecision (26).

For Most individuals should Different choices will be

clinicians receive the intervention. appropriate for individual
Formal decision aids are not patients consistent with his or Inulin
likely to be needed to help her values and preferences. Summary of evidence. Two studies assessed the effect of inulin for
individuals make decisions Use shared decision making. the treatment of CIC (27,28). The first study was a randomized
consistent with their values Decision aids may be useful in placebo-controlled study conducted in Brazil involving 60 female
and preferences. helping patients make participants aged 18–65 years with at least 3 months of constipation
decisions consistent with their and ,3 bowel movements per day (27). Twenty-eight patients were
individual risks, values, and in the fiber group and 32 in the placebo group (27). Participants were
preferences. given 4 days to adapt to the mixture of inulin and partially hydro-
For policy The recommendation can be Policy making will require
lyzed guar gum or placebo before beginning a 3-week treatment with
makers adapted as policy or substantial debate and
either 15g/d of inulin or 15 g/d of maltodextrin (placebo) that was
performance measure in involvement of various
divided into 3 sachets of 5 g each (27). The second study was con-
most situations. stakeholders. Performance
ducted in Belgium on participants aged 50–70 years who were
measures should assess
randomized to 7.5 g of inulin sachet and placebo for 28 days (28).
whether decision making is
The inulin and placebo groups included 25 participants each. The
appropriate.
duration of follow-up was 28 days.
Benefits and harms. All included studies did not contribute data for
our outcomes of interest. Based on one small study, treatment with
inulin had little to no effect on SBMs per week (MD 20.75, CI 22.60
FIBER to 1.10) and responder rate, defined as .3 CSBMs per week (RR 1.21,
CI 0.83–1.74) (27). Regarding side effects, no serious adverse events
were reported, although a minor side effect of flatulence occurred
Recommendation 1: In adults with CIC, the panel suggests the use of
fiber supplementation over management without fiber supplements more frequently in the inulin group, according to one study (28).
(conditional recommendation, low certainty of evidence). There were no data on CSBMs per week, diarrhea, serious adverse
Implementation considerations effects, quality of life, or stool form.
· Dietary assessment is important to determine total fiber intake
from diet and supplements.
Certainty in evidence of effects. We are very uncertain about the
effects of inulin. The certainty of evidence for the effect of inulin
· Fiber supplements can be used as first-line therapy for CIC,
particularly for individuals with low dietary fiber intake.
on SBMs and the responder rate was very low and low, re-
spectively, because of concerns about risk of bias and imprecision
· Among the evaluated fiber supplements, only psyllium appears to
be effective (with very limited and uncertain data on bran and inulin).
because of the small number of included participants in the study.

·· Adequate hydration should be encouraged with the use of fiber.

Flatulence is a commonly observed side effect with the use of
fiber.
We evaluated evidence for fiber supplementation in the form
of bran, inulin, psyllium, and methylcellulose. The overall cer-
tainty of evidence for the use of fiber in the management of CIC
compared with management without fiber was low. No studies
were found on the use of methylcellulose, but data on bran, inulin,
and psyllium are outlined below.
Bran
Summary of evidence. One randomized study conducted in Italy
with a cross-over design evaluated the efficacy and safety of bran in
29 patients with chronic nonorganic constipation (26). Participants
received either a ground bran (6.6 g) or an identical-looking prep-
aration of placebo 3 times a day for two 4-week periods (26).
Psyllium
Summary of evidence. Three RCTs conducted between 1986 and
1995 studied psyllium vs placebo (29–31). Psyllium was evaluated
in a small study from the United States that included 22 adult
participants with CIC confirmed by prospectively administered
stool diaries (29). Constipation was defined as ,3 bowel move-
ments per week. A 4-week baseline phase was followed by 8 weeks
of double-blinded treatment, during which patients received ei-
ther 5 g twice daily of psyllium or placebo, followed by a 4-week
washout period (29). The second study included 201 participants
with functional constipation between 18 and 70 years (30). Par-
ticipants were randomly allocated to either Regulan (a refined
hydrophilic mucilloid derived from psyllium seed husks) or
matching placebo for 14 days (30). Participants received one sa-
chet (containing 3.6 g of active ingredient) of either psyllium or
placebo 3 times daily (30). A third study included 35 participants
with constipation who were randomized to receive either

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 Clinical Practice Guidelines 7
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Figure 1. PRISMA flow diagram. Six studies on fiber supplements included studies on the use of insulin (1 study), bran (1 study), and psyllium (3 studies).
One study addressed magnesium oxide and senna in the same trial, so the total number of included studies is 28 and not 29. PEG, polyethylene glycol.

© 2023 by The American College of Gastroenterology and the American Gastroenterological Association The American Journal of GASTROENTEROLOGY
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8
The American Journal of GASTROENTEROLOGY

Chang et al
Table 4. Overview of interventions for the pharmacological management of chronic idiopathic constipation

What medications can be

used to treat chronic
idiopathic constipation? Mechanism of action
Fiber Soluble fiber traps water in the
intestine and softens stool
Insoluble fiber increases stool
bulk
Polyethylene glycol Osmotic laxative
Magnesium oxide Osmotic laxative
Lactulose Osmotic laxative
Bisadocyl and picosulfate Stimulant laxative
VOLUME 00 | MONTH 2023 www.amjgastro.com
Recommended initial dose
The Academy of Nutrition
and Dieteticsa recommends
14 g/1,000 kcal intake per day
Total daily fiber intake (dietary
1 supplement) 20–30 g/d
17 g daily
400–500 mg daily
15 g daily
Bisacodyl 5 mg daily
Guidance for dose titration
Per response to symptoms
and side effects
Common side effects
include bloating and
abdominal discomfort
Per symptom response and
side effects
Common side effects include
bloating, abdominal
discomfort, and cramping
Per symptom and response
and side effects
Per symptom response and
side effects
Bloating and flatulence may
be limiting if preexisting
symptoms or at higher doses
Per symptom response and
side effects
Side effects limited by
Maximum dose
Usually no benefit to
increasing total fiber intake
over 25–30 g
No clear maximum dose
No clear maximum dose. Prior ,$50
studies used 1,000–1,500 mg
daily
No clear maximum dose. May ,$50
cause hypernatremia and
hypokalemia if patients
experience significant
diarrhea
10 mg orally daily
Estimated monthly
cost, USDa Additional comments
,$50 Ensure adequate hydration as
fiber intake increases
No clear evidence that soluble
or insoluble fiber is more
effective
Soluble fiber includes
psyllium, inulin, oats, fruit,
barley, and legumes
Insoluble fiber includes wheat
bran, methylcellulose, wheat,
rye, and other grains
$10-$45 Response to PEG has been
shown to be durable over 6 mo
Use with caution in patients
with renal insufficiency and in
pregnancy
Only osmotic agent studied in
pregnancy
,$50 Recommended for short-term
use or rescue therapy
Prolonged or excessive use

cramping and abdominal can cause diarrhea and

discomfort
Senna Stimulant laxative 8.6–17.2 mg daily Per symptom response and
side effects
Side effects most commonly
cramping and abdominal
discomfort
No clear maximum dose.
Often recommended
maximum is 4 tablets twice per
day
electrolyte imbalance
Long-term safety and efficacy
unknown
,$50 Also present in many laxative
teas, where dose may be
difficult to calculate
Long-term safety and efficacy
unknown
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Table 4. (continued)

What medications can be

used to treat chronic Estimated monthly
idiopathic constipation? Mechanism of action Recommended initial dose Guidance for dose titration Maximum dose cost, USDa Additional comments
Lubiprostone Intestinal secretagogue acting 24 mg BID Per symptom response 24 mg BID $374 May have benefit for
on chloride channel type 2 in Diarrhea may occur in a abdominal pain. Also
the gut that increases chloride subset of patients, leading to approved for the treatment of
secretion discontinuation IBS-C at a dose of 8 mg BID
Linaclotide Intestinal secretagogue acting 72–145 mg daily Per symptom response 290 mg daily $523 May have benefit for
on guanylate cyclase-C, which Diarrhea may occur in a abdominal pain. Also
activates CFTR in the gut to subset of patients, leading to approved for the treatment of
increase chloride secretion discontinuation IBS-C
Plecanatide Intestinal secretagogue acting 3 mg daily Per symptom response 3 mg daily $526 Also approved for the
on guanylate cyclase-C, which Diarrhea may occur in a treatment of IBS-C
activates CFTR in the gut to subset of patients, leading to
increase chloride secretion discontinuation
Prucalopride 5-HT4 agonist 1–2 mg daily Per symptom response 2 mg daily $563 May have additional benefit for
Headaches and diarrhea abdominal pain
may occur in a subset of
patients, leading to
discontinuation

5-HT4, serotonin type 4; BID, twice a day; IBS-C, irritable bowel syndrome with constipation; PEG, polyethylene glycol; USD, US dollar.
a
The given cost accommodates the extent of generic and prescription medications and may not be the exact cost. In addition, the given cost is not the cost-effectiveness of the medication, but a probable cost per month.
The American Journal of GASTROENTEROLOGY

Clinical Practice Guidelines

9
 10 Chang et al
celandine-aloe vera-psyllium or placebo (31). Capsules of 500 mg
contained the active ingredients celandine, aloe vera, and psyl-
lium in the ratio of 6:3:1. The initial dose was 1 capsule per day,
taken with water at bedtime, and increased to 3 capsules per day
depending on the response (31).
Benefits and harms. Based on the meta-analysis of data from 3
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studies (29–31), the use of psyllium may lead to an increase in
SBMs per week (MD 2.32, CI 0.86–3.79). Combined data from 2
studies showed that the use of psyllium may increase global relief
symptoms (RR 1.86, CI 1.49–2.30), but there was little to no
difference in stool consistency (MD 21.08, CI 21.33 to 0.83)
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(30,31). In absolute terms, psyllium was associated with 391 per
1,000 more individuals with global relief (from 223 more to 591
more). One study (30) examined withdrawal from the study be-
cause of diarrhea but with only 3 events; the summary estimate
was too imprecise to make any conclusive statement (RR 0.47, CI
0.04–5.06); and no serious adverse events were reported in either
arm. There were no data on CSBMs per week, responder rate,
diarrhea, quality of life, or stool form.
Certainty in evidence of effects. The certainty of evidence for
SBM, serious adverse events, and global relief was low and for
diarrhea, was very low. We rated down certainty of evidence
because of high risk of bias (concerns about methods of ran-
domization and allocation concealment in 2 studies and high
attrition in another study), indirectness, and imprecision.
Discussion
Fiber can be divided into soluble and insoluble fiber. Wheat bran,
an insoluble fiber, is produced when the hard outer fiber of the
wheat kernel is removed during the refining process. Inulin is a
naturally occurring polysaccharide present in many plants and
most often extracted from chicory. Inulin is a fructan and is
considered both a soluble fiber and a prebiotic, meaning that it
can stimulate the growth or activity of intestinal bacteria (32) that
are believed to promote good gut health. Psyllium is also con-
sidered to be a soluble fiber and may also have prebiotic potential
(33). Fiber has been recognized as important for normal laxation,
primarily because it increases stool weight, and this has the sec-
ondary effect of reducing transit time. Fiber increases stool weight
by its presence but also by increasing the water held by the fiber, as
well as increasing bacterial mass from fermentation. However,
inulin does not increase stool weight to the extent that wheat bran
and psyllium do, but does undergo extensive fermentation (32).
Fiber is often recommended as a therapy to supplement dietary
intake of fiber. However, as the studies above indicate, there are
different formulations and types of fibers that have been evaluated
and the included studies did not quantify the intake of dietary fiber.
At least 2 studies were conducted with fiber that contained other
ingredients such as milk or aloe vera that may additionally influence
laxation. All studies are 30–40 years old, and the number of partic-
ipants in the studies has been small and most are primarily con-
ducted in women. Most of the included studies on fiber
supplementation did not report on relevant patient important out-
comes. The best data exist for psyllium, but even those are of low
quality. In addition, wheat bran can exist as a finely ground powder
that can decrease stool water content and harden stool (34). The chief
side effect of fiber supplementation seems to be flatulence. In indi-
viduals with mild-to-moderate symptoms of constipation, especially
who consume diets deficient in fiber, a trial of fiber supplementation
is warranted because it is low-risk, low-cost, and easily accessible.
In general, chronically constipated patients and nonconstipated
The American Journal of GASTROENTEROLOGY
persons drink similar amounts of fluid on a daily basis. However,
when individuals are placed in quartiles based on daily fluid intake,
those in the lowest quartile for fluid intake are more likely to be
constipated. Thus, efforts to increase fluid intake should be focused
on those with low levels of fluid intake (35). Standard doses of fiber
supplements are typically taken with 8–10 ounces of fluid (36).
OSMOTIC LAXATIVES
Recommendation 2: In adults with CIC, the panel recommends the
use of PEG compared with management without PEG (strong
recommendation, moderate certainty of evidence).
Implementation considerations
· A trial of fiber supplement can be considered for mild
constipation before PEG use or in combination with PEG.
·· Response to PEG has been shown to be durable over 6 months.
Side effects include abdominal distension, loose stool,
flatulence, and nausea.
Polyethylene glycol
Summary of evidence. Three randomized, placebo-controlled trials
studied the effect of PEG on constipation (37–39). Two of these studies
were multicenter trials conducted in Italy and enrolled participants
aged 18–70 years with chronic constipation defined in accordance
with the Rome criteria, that is, less than 2 bowel movements per week
for at least 12 months or the presence of 2 or more of the following
symptoms: ,3 bowel movements per week, straining at defecation,
sense of incomplete evacuation, and hard stools on at least 25% of
occasions (37,38). In both trials, the treatment consisted of 17.5 g of
PEG with electrolytes as a granular preparation or placebo dissolved in
250 mL of water taken twice daily. One study included 55 participants,
and the treatment period lasted 8 weeks (38). The second study (37)
included 70 participants and had 2 consecutive periods in which all
participants received the active treatment, PEG for 4 weeks, and then
those who responded were randomized to receive either PEG or
placebo for 20 weeks. The third study was conducted in the United
States and included 304 participants with chronic constipation based
on modified Rome criteria, where participants reported ,3 bowel
movements per week for at least 3 months and one or more of the
following: straining, lumpy or hard stools, and sensation of incomplete
evacuation in .25% of defecations (39). Participants were random-
ized in a 2:1 ratio to PEG 3350 (n 5 204) at a dose of 17 g or placebo (n
5 100) mixed in 8 ounces of liquid once daily for 6 months.
Benefits and harms. PEG likely results in an increase in CSBMs
per week compared with placebo (MD 2.90, CI 2.12–3.68), based
on one study (39), and SBMs per week (MD 2.30, CI 1.55–3.06),
based on meta-analyzed data from 3 studies (37–39). Across 2
studies, a higher rate of individuals met the responder definition,
one study defined responder as normalization of bowel moments
(37,38) and other defined based on the US Food and Drug Ad-
ministration (FDA) end points (40), compared with placebo (RR
3.13, CI 2.00–4.89); PEG was associated with 312 more per 1,000
(from 146 more to 569 more). Diarrhea was noted more com-
monly in the treatment arm (158 more per 1,000, from 6 fewer to
896 more). A higher proportion of participants had global relief of
symptoms with PEG compared with placebo with 454 per 1,000
in the PEG group (from 159 more to 948 more). There were no
data for the following outcomes: stool form and quality of life.
Two studies examined serious adverse events, but the number of
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events was very small, and no conclusive statements could be
made about risk of serious adverse events with the use of PEG (RR
0.47, CI 0.16–1.33).
Certainty in evidence of effects. The certainty of evidence for
CSBMs, SBMs, responder rate, and global relief was moderate
(because of imprecision). The certainty of evidence for serious
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adverse events was low because the CI includes both low and high
risk of serious adverse events. The overall certainty of evidence for
PEG was moderate.
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Discussion
PEG is a long-chain polymer of ethylene oxide, which acts as an
osmotic laxative. PEG is approved at a dose of 17 g daily for the
treatment of occasional constipation by the FDA in the United
States and is widely available OTC. Two of the studies used PEG
with electrolytes given twice daily (37,38) while the other larger
study evaluated the efficacy of PEG 3350 without electrolytes ad-
ministered once daily (39). The 2 studies of PEG 3350 electrolytes
measured the frequency of SBMs per week, but not CSBMs per
week (37,38), while the PEG 3350-only study measured CSBM and
SBM frequency along with other outcomes (39). Despite the dif-
ferences in the PEG preparations, doses, and treatment durations,
the studies all demonstrated that PEG was associated with a greater
efficacy in increasing CSBMs, SBMs, responder rate, improve-
ments in stool form, straining, and global relief compared with
placebo, but not abdominal pain. Although PEG is approved by the
FDA for the treatment of occasional constipation and not CIC, it
has been shown to be efficacious in individuals with CIC for up to 6
months (39). There are additional treatment trials comparing the
efficacy of PEG with tegaserod, prucalopride, and lactulose, in
which PEG demonstrated a similar or greater efficacy in individuals
with CIC than these other medications (41,42), although these
trials used different primary end points.
There were no differences in side effect profiles observed be-
tween PEG and placebo, although data are limited. Individuals
treated with PEG may experience bloating, flatulence, and di-
arrhea. These effects are consistent with and expected from lax-
ative therapy, and most of these events were mild or moderate.
However, PEG is widely available without the need for a pre-
scription and is relatively inexpensive. It is, therefore, reasonable
to use PEG earlier in the algorithm for the management of CIC,
either after a trial of fiber supplementation or in combination with
fiber supplementation.
Recommendation 3: In adults with CIC, the panel suggests the use
of MgO over management without MgO (conditional
recommendation, very low certainty of evidence certainty).
Implementation considerations
· The trials were conducted for 4 weeks, although longer term use
is probably appropriate.
· The panel suggests starting at a lower dose, which may be
increased if necessary.
· Avoid use in patients with renal insufficiency due to risk of
hypermagnesemia.
Magnesium oxide
Summary of evidence. Two randomized, placebo-controlled
trials evaluated the use of MgO for the management of CIC
© 2023 by The American College of Gastroenterology and the American Gastroenterological Association
Clinical Practice Guidelines 11
(43,44). Both trials were completed in Japan. The dose of MgO
studied was 1.5 g/d for 4 weeks. The 2 trials randomized a total
of 47 participants to MgO and 47 participants to the placebo
arm, and 93% of the participants were females. At baseline,
participants randomized to the placebo group had 4.6 SBMs
per week. Those randomized to MgO had 4 SBMs per week at
baseline.
Benefits and harms. Compared with placebo, treatment with
MgO may increase the number of CSBMs per week (MD 4.29,
95% CI 2.93–5.65) and SBMs per week (MD 3.59, 95% CI
2.64–4.54). Participants treated with MgO achieved a higher
treatment response compared with placebo (RR 3.93, 95% CI
2.04–7.56). In absolute terms, 499 more participants per 1,000
might respond to MgO (from 177 to 1,000 more). There was
little to no difference in the degree of diarrhea leading to
treatment dose change or discontinuation between the 2 study
groups (RR 1.07, 95% CI 0.65–1.74). Participants treated with
MgO may have better quality-of-life scores as measured by
PAC-QOL (MD 16.23, 95% CI 11.44–21.01) and better stool
consistency based on the Bristol Stool Form Scale (MD 1.89,
95% CI 1.44–2.33).
Certainty in evidence of effects. The certainty of evidence was
very low for the outcomes of CSBMs per week and SBMs per
week because of concerns related to inconsistency, in-
directness, and imprecision. The certainty of evidence was
moderate for the outcomes of responder rate and adverse
events due to diarrhea because of imprecision and in-
consistency, respectively. The outcomes of quality of life and
stool form were rated as low certainty because of indirectness
and imprecision. The overall certainty of evidence for MgO
was very low.
Discussion
Magnesium is a naturally occurring element that plays an
important role in a wide range of biological and biochemical
processes (45). Within the lumen of the GI tract, nonabsorbed
magnesium creates an osmotic gradient, which leads to net
secretion of water and electrolytes, which can exert a benefi-
cial effect on constipation-related symptoms. MgO dosing in
the available RCTs was 1.5 g/d. Although not studied in RCTs,
lower MgO doses of 500 mg/d to 1 g/d are often used in clinical
practice. Only MgO has been evaluated in RCTs; the bio-
availability and clinical efficacy of other formulations of
magnesium (e.g., citrate, glycinate, lactate, malate, sulfate) for
CIC are unknown. Data on adverse effects of MgO from the
available trials are limited. The available data suggest no in-
creased reports of diarrhea with MgO compared with placebo
(43). Systemic regulation of magnesium levels is maintained by
renal excretion (46). Therefore, hypermagnesemia is more
likely to occur in individuals with significant renal impairment
and magnesium supplements should be avoided in those with a
creatinine clearance of ,20 mg/dL (47).
The combination of efficacy, tolerability, availability of OTC,
and low cost make MgO an attractive first-line option for indi-
viduals with CIC. Limitations to consider include the small
number of clinical trials and included participants with CIC, all
trials being conducted in Japan, formulations other than MgO not
being evaluated, the dose of MgO used in trials being higher than
The American Journal of GASTROENTEROLOGY
 12 Chang et al
that typically used in clinical practice, and no long-term effec-
tiveness or harms data being available.
Recommendation 4: In adults with CIC who fail or are intolerant to
OTC therapies, the panel suggests the use of lactulose over
management without lactulose (conditional recommendation,
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very low certainty of evidence).
Implementation considerations
· Bloating and flatulence are dose-dependent and common side
effects, which may limit its use in clinical practice.
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Lactulose
Summary of the evidence. Two RCTs studied the efficacy of lac-
tulose syrup for the treatment of CIC in elderly participants (48,49).
One multicenter study performed in the Netherlands included 103
participants who were regularly taking laxatives for the treatment
of chronic constipation (49). The initial dose of 15 mL of either 50%
lactulose syrup or 50% glucose syrup was administered daily for a
total of 3 weeks. The daily dose was reduced by half after 3 con-
secutive days with defecation, but if no defecation occurred for
more than 48 hours, the dose was doubled. If defecation occurred
on 3 consecutive days with the doubled dose, the dose was reduced
back to 15 mL (49). The second study, conducted in the United
States, included 55 constipated participants (48). Participants re-
ceived 30 mL daily of either 50% lactulose syrup or 50% glucose
syrup, taken at bedtime for 12 weeks (48).
Benefits and harms. Based on one study, lactulose may have
little to no effect on SBMs per week (MD 0.35, CI 20.91 to
1.61). A second study, however, showed that lactulose may be
associated with a large increase in global relief (RR 2.42, CI
1.29–4.54, in absolute terms, 473 more per 1,000, CI 97 more to
1,000 more). Across the 2 studies, there was a higher rate of
individuals taking lactulose who met the responder definition
(defined as .1 SBM from baseline in 1 study and lack of need of
other laxatives in other study) compared with placebo. Lac-
tulose was associated with 267 more per 1,000 (from 108 more
to 471 more) responders. The studies did not report on CSBMs
per week, diarrhea, serious adverse events, quality of life, or
stool form.
Certainty in evidence of effects. The certainty of evidence for
SBMs was very low because of risk of bias (unclear methods of
randomization and blinding) and imprecision. The certainty
of evidence for global relief and responder rate was low because of
concerns for risk of bias and imprecision. The overall certainty of
evidence for lactulose was very low.
Discussion
Lactulose is b-galactosido-fructose, a synthetic disaccharide
not digested in the small intestine that exerts an osmotic
laxative effect in the colon to promote peristalsis. It is ap-
proved by the FDA in the United States for the treatment of
constipation at a dose of 10–20 g (15–30 mL or 1–2 packets)
daily and is widely available in other countries. The dose may
be increased to 40 g (60 mL or 2–4 packets) daily if needed.
There were significant limitations in the 2 RCTs of lactulose;
both trials were conducted over 40 years ago, included rela-
tively small numbers of elderly participants, and did not re-
port the diagnostic criteria for constipation (48,49). In the US
study, most participants were women living in a nursing
home and medical facility and the mean age was in the mid-
The American Journal of GASTROENTEROLOGY
80s (48). Bowel movement frequency and the severity of
symptoms improved to a greater degree in the lactulose group
compared with the glucose group. Interestingly, the most
dramatic finding was the decrease in impactions and need for
enemas in individuals receiving lactulose. The other study
from the Netherlands did not report demographics of the
patient population.
There were minimal data on adverse events from the 2 pub-
lished studies (48,49); however, bloating and flatulence (which are
dose-dependent) are considered very common side effects of
lactulose in clinical practice, which limit its use. Some brands of
lactulose may be expensive, although generic lactulose is generally
low cost. Lactulose can be considered if symptoms of CIC have
failed to improve with fiber and OTC laxatives, and individuals do
not experience significant bloating or abdominal pain with lac-
tulose use. The use of lactulose in mildly constipated, noninsulin-
dependent patients with diabetes mellitus type 2 may not lead to
increase in blood sugar levels (50).
STIMULANT LAXATIVES
Recommendation 5: In adults with CIC, the panel recommends the
use of bisacodyl or sodium picosulfate (SPS) short term or as
rescue therapy over management without bisacodyl or SPS
(strong recommendation, moderate certainty of evidence).
Implementation considerations
· Short-term use is defined as daily use for 4 weeks or less. While
long-term use is probably appropriate, data are needed to better
understand tolerance and side effects.
· This is a good option for occasional use or rescue therapy in
combination with other pharmacological agents for CIC.
· The most common side effects are abdominal pain, cramping
and diarrhea. The panel suggests starting at a lower dose and
increasing the dose as tolerated.
Summary of evidence. The panel considered studies that eval-
uated bisacodyl and SPS, which are mechanistically related, for
the management of CIC. Of note, SPS tablets/drops are not
available for use in the United States; however, they are ap-
proved for use in Europe. In the United States, SPS is available
in combination with other laxatives and used for bowel prep-
aration before colonoscopy. Given their common mechanism
of action and limited number of trials on these drugs in
treatment of CIC, the data from available trials were pooled in
calculations of estimates of effect. A total of 2 studies were
included. One of these studies was a multicenter randomized
double-blinded placebo-controlled trial in the United King-
dom where recruited participants were assigned in a 2:1 ratio
to bisacodyl (n 5 247) vs placebo (n 5 121) and treated for 4
weeks (51). The other study examined effects of SPS in a
multicenter double-blinded placebo-controlled RCT con-
ducted in Germany, and participants were randomized in a 2:1
ratio to SPS (n 5 229) or placebo (n 5 133) and treated for 4
weeks (52).
Benefits and harms. Based on meta-analyzed data from 2 studies,
SPS likely leads to a large increase in CSBMs per week (MD 2.54,
95% CI 1.07–4.01) and SBMs per week (MD 4.04, 95% CI
2.37–5.71) and improved the consistency of stool on the
Bristol Stool Form Scale (53) (MD 2.4 points higher, 95% CI
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2.07–2.73) and PAC-QOL scores (MD 0.65, 95% CI
0.50–0.80) compared with placebo. Furthermore, the use of
SPS leads to higher responder rates (RR 2.60, 95% CI
2.05–3.30) and an increased proportion of individuals with
global relief (RR 1.75, 95% CI 1.48–2.07). In absolute terms, of
1,000 individuals treated with SPS, there would be 359 more
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responders (236 more to 516 more) and 357 more with global
relief (228 more to 509 more). Use of SPS may increase the
proportion of individuals who experience diarrhea compared
with placebo (RR 8.76, 95% CI 4.99–15.39). One study
reported serious adverse events but with only 3 events, results
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were very imprecise (RR 0.24, 95% CI 0.02–2.67). The rate of
diarrhea leading to discontinuation of treatment was higher
in the SPS group compared with placebo (RR 8.76, 95% CI
4.99–15.39).
Certainty in evidence of effects. The certainty of evidence was
rated as moderate for the following outcomes: CSBM and
SBM frequency, responder rate, global relief, and stool con-
sistency (because of risk of bias). The certainty of evidence
was very low for the outcomes of diarrhea and serious adverse
events (because of risk of bias, indirectness, and imprecision)
and low for quality of life (because of risk of bias and in-
directness). The overall certainty of evidence for bisacodyl
was moderate.
Discussion
Bisacodyl and SPS are converted in the gut into the same active
metabolite, bis-(phydroxyphenyl)-pyridyl-2-methane (BHPM).
Bisacodyl is converted into BHPM by small bowel and colonic
mucosal deacetylase enzymes while SPS is converted into BHPM
by colonic bacteria desulfate enzymes. BHPM acts directly on the
colonic mucosa to stimulate colonic peristalsis and secretion.
Similar to other stimulant laxatives (e.g., senna), use of antibiotics
can potentially decrease the efficacy of SPS because they may
affect colonic bacteria that produce the active metabolite of the
drug (54).
Initial dosing in the available RCTs was 10 mg orally for
bisacodyl and SPS, although dose reduction was permitted. At
this dose, adverse effects were common (see below), and
therefore in clinical practice, 5 mg orally is often used initially.
Although not studied in RCTs, bisacodyl is also available as a
rectal suppository (10 mg). The onset of action is typically 6–12
hours for the oral tablet while the suppository works within
30–60 minutes.
The most common adverse effects for bisacodyl and SPS were
diarrhea and abdominal pain. For bisacodyl at the initial starting
dose of 10 mg compared with placebo, diarrhea occurred in
53.4% vs 1.7%, respectively, while abdominal pain occurred in
24.7% vs 2.5%, respectively (51). Most adverse events occurred
in the first week of treatment. For SPS at the initial starting dose
of 10 mg compared with placebo, diarrhea was reported by
31.8% vs 4.5%, respectively, while for abdominal pain, it was
reported by 5.6% vs 2.2%, respectively (52). Bisacodyl and SPS
are contraindicated in individuals with ileus, intestinal ob-
struction, severe dehydration, or acute inflammatory conditions
in the bowel.
Although effective, side effects are common, and the panel
recommended the use of bisacodyl and SPS for a short term or
© 2023 by The American College of Gastroenterology and the American Gastroenterological Association
Clinical Practice Guidelines 13
rescue therapy. The long-term effectiveness of these agents has
not been studied.
Recommendation 6: In adults with CIC, the panel suggests the use
of senna over management without senna (conditional
recommendation, low certainty of evidence).
Implementation considerations
· While the trials were conducted for 4 weeks, longer term use is
probably appropriate, but data are needed to better understand
tolerance and side effects.
· The dose evaluated in trials is higher than commonly used doses
in practice. The panel suggests starting at a lower dose and
increase if there is no response.
· Abdominal pain and cramping may occur with a higher dose of
senna.
Senna
Summary of evidence. One placebo-controlled RCT examined
the safety and efficacy of senna in the management of CIC (44).
Participants were randomly assigned to 1 g of senna (n 5 30) or
placebo (n 5 30) and treated for 28 days.
Benefits and harms. Participants treated with senna may have
higher CSBMs per week (MD 7.60, 95% CI 5.90–9.30) and SBMs
per week (MD 7.6, 95% CI 6.42–8.78) compared with the placebo
group. The response rate might be higher in the senna-treated
group compared with placebo (RR 5.25, 95% CI 2.05–13.47), 567
more per 1,000 in the senna group (from 140 to 1,000 more). The
quality-of-life scores may be higher in the senna group compared
with placebo (MD 7.80, 95% CI 1.40–14.20). Participants taking
senna might have higher rates of diarrhea, 175 more per 1,000
(from 100 fewer to 1,000 more). No participants in the senna and
placebo arms experienced a severe treatment-related adverse event.
Certainty in evidence of effects. The certainty of evidence was low
for the outcomes of CSBMs per week, SBMs per week, and quality
of life as the panel rated down because of concerns for in-
directness and imprecision. The certainty of evidence for re-
sponder rate was moderate because of imprecision. The overall
certainty of evidence for senna was low.
Discussion
Senna is a natural derivative of the senna plant. Sennosides A and B
are sequentially metabolized by the gut microbiota to the active
metabolites, rheinanthrone and rhein, which stimulate the pro-
duction of prostaglandin E2 and secretion of chloride ions leading to
attendant changes in colonic peristalsis and luminal water content
(55,56). Over 90% of sennosides and their metabolites are excreted in
the feces (56). Dosing in the single RCT published to date was 1 g by
mouth daily for 4 weeks, which is higher than that typically used in
clinical practice. It is notable that while no details were provided, 83%
of participants randomized to senna reduced their daily dose during
the trial (44). Most commercially available senna products contain
8–9 mg per tablet. Rigorous dose ranging data with senna are cur-
rently not available. In the clinical trial by Moshita et al. (44), no
participants experienced a severe treatment-related adverse event.
However, as Moshita et al. (44) did not provide rates for the mild
treatment-related adverse events, the fact that 83% of participants
The American Journal of GASTROENTEROLOGY
 14 Chang et al
with CIC randomized to senna engaged in dose reduction raises
concerns about potential adverse events such as abdominal pain,
cramping, or diarrhea with the higher dose of senna. There are no
long-term safety studies with senna in humans. Sennosides are not
recommended in pregnant women because chemically similar sub-
stances have been found to exert weak genotoxic effects in animals,
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although the supporting evidence is controversial (57).
The combination of efficacy, impact on quality of life, avail-
ability OTC, and low cost makes senna an attractive first-line op-
tion for individuals with CIC. Limitations to consider include the
following: only a single, small RCT from Japan supports its efficacy;
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the dose of senna used in the trial is higher than that typically used
in clinical practice; there are no long-term effectiveness data; and
very limited short-term and no long-term harms data are available.
SECRETAGOGUES
Recommendation 7: In adults with CIC who do not respond to OTC
agents, the panel suggests the use of lubiprostone over
management without lubiprostone (conditional
recommendation, low certainty of evidence).
Implementation considerations
·· Can be used as a replacement or as an adjunct to OTC agents.
Duration of treatment in trials was 4 weeks, but the drug label
does not provide a limit.
· Nausea may occur; however, the risk of nausea is dose-
dependent and seems to be lower when taken with food and
water.
Lubiprostone
Summary of evidence. Three 4-week randomized double-blinded
placebo-controlled trials evaluated the use of lubiprostone for the
management of CIC (58–60). The studied dose of lubiprostone
was 24 mg twice daily, and studies were conducted in the United
States and Japan. Lubiprostone is a chloride channel activator,
resulting in increased intestinal fluid and accelerated GI transit.
Benefits and harms. The pooled data showed that lubiprostone
resulted in an increased number of SBMs per week compared
with placebo (MD 1.98, 95% CI 1.17–2.79). The data for the
outcome of CSBMs per week were not available. Use of lubipro-
stone in adults with CIC may increase responder rates (RR 1.67,
95% CI 1.36–2.06), 226 more per 1,000 (from 122 to 358 more).
Individuals may also be at increased risk of diarrhea leading to
discontinuation of the treatment compared with placebo (RR
5.30, 95% CI 1.53–18.44), 28 more per 1,000 (from 4 more to 115
more). There was little to no difference in serious adverse events;
however, the CI around the summary estimate was wide, and
increased risk of serious adverse events could not be ruled out (RR
1.22, 95% CI 0.62–2.42). The data on quality of life from the
available studies were not reported. Stool form, using a 0- to 4-
point scale (very loose to very hard, where a lower score is better),
was evaluated in 2 studies and improved in the lubiprostone
group (MD 1.09 lower, 95% CI 0.16–2.03 lower). Finally, the rate
of global relief, evaluated in one study using a 0- to 4-point scale
(not effective to very effective, where higher is better), was higher
in the lubiprostone group (MD 0.75, 95% CI 0.42–1.08 higher).
Certainty in evidence of effects. The certainty of evidence was
moderate for the outcome of SBMs per week (because of impre-
cision) and low for the remainder of the outcomes (because of
The American Journal of GASTROENTEROLOGY
very serious imprecision). The overall certainty in evidence for
lubiprostone was low.
Discussion
Lubiprostone, a bicyclic fatty acid derived from prostaglandin E1
that increases intestinal chloride secretion by activating type 2
chloride channels on epithelial cells, is approved by FDA for
treating CIC at a dose of 24 mg 2 times daily. For IBS-C, the
approved dose is 8 mg 2 times daily. Lubiprostone improved stool
frequency and consistency as well as abdominal discomfort and
bloating, which is a bothersome symptom in some individuals
with CIC (60,61). Among individuals who respond, these effects
generally manifest within 2 days. The efficacy in persons 65 years
and older is comparable with the overall study population.
Lubiprostone accelerates small intestinal and colonic transit in
healthy people (62), should be taken with meals, and is contra-
indicated in individuals with known or suspected mechanical GI
obstruction. Observed in 35% of individuals, nausea was the most
common adverse event and typically mild or moderate, but led to
discontinuation of therapy in only 5% of individuals (60). The risk
of nausea is dose-dependent and seems to be lower when taken
with food and water (63).
Systemic absorption of oral lubiprostone is negligible. Indi-
viduals with moderate or severe hepatic insufficiency should re-
ceive a lower dose (i.e., 8 mg twice daily).
Recommendation 8: In adults with CIC who do not respond to OTC
agents, the panel recommends the use of linaclotide over
management without linaclotide (strong recommendation,
moderate certainty of evidence).
Implementation considerations
·· Can be used as a replacement or as an adjunct to OTC agents
Duration of treatment in trials was 12 weeks, but the drug label
does not provide a limit.
· May be associated with side effects of diarrhea leading to
discontinuation of treatment
Summary of evidence. Three 12-week randomized double-
blinded placebo-controlled trials evaluated the use of linaclotide for
the management of CIC (10,64). The studied doses of linaclotide
were 145 and 290 mg daily, and all studies were conducted in the
United States and Canada. The following dose has also been
studied (72 mg) (65). Linaclotide is a guanylate cyclase-C agonist,
which increases cyclic guanosine monophosphate concentrations
resulting in luminal chloride and bicarbonate secretion, thereby
increasing intestinal fluid and accelerating GI transit.
Benefits and harms. The use of linaclotide leads to increases in
the number of CSBMs per week (MD 1.37, 95% CI 1.07–1.95) and
SBMs per week (MD 1.97, 95% CI 1.59–2.36), improves stool
consistency (MD 1.25, 95% CI 1.1–1.39 higher), and increases the
rates of global relief (RR 1.96, 95% CI 1.63–2.35). The use of
linaclotide might lead to a large increase in responder rates
compared with placebo (RR 3.14, 95% CI 1.68–5.88), 119 more
per 1,000 (from 38 to 271 more). However, participants treated
with linaclotide might be 3 times more likely to have diarrhea
leading to treatment discontinuation compared with placebo (RR
3.35, 2.09–5.36), 83 more per 1,000 (from 38 to 154 more). The
use of linaclotide might improve the PAC-QOL scores compared
with placebo (64); however, data could not be pooled.
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Certainty in evidence of effects. We rated the certainty of evi-
dence as high for outcomes of CSBMs per week, SBMs per week,
stool form, and global relief and moderate for the responder
outcome and diarrhea (rating down for imprecision). The out-
come of serious adverse events was rated down to low because of
very serious imprecision. The overall certainty of evidence for
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linaclotide was moderate.
Discussion
Linaclotide is a guanylate cyclase-C agonist FDA-approved for the
treatment of CIC at a dose of 72 mg or 145 mg daily. The 290 mg
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daily dose is approved for IBS-C, recognizing that CIC and IBS-C
overlap and are often indistinguishable in practice (66). Linaclotide
is also approved in many other countries. Linaclotide has been
demonstrated to improve abdominal symptoms of bloating, dis-
comfort, and pain in IBS-C trials (67). Because of its effect on
abdominal discomfort, pain, and bloating, it may be useful in in-
dividuals with these coexisting symptoms. Patients should be
instructed to take linaclotide without food, at least 30 minutes
before the first meal of the day. Linaclotide is contraindicated in
individuals with known or suspected mechanical GI obstruction.
The use of linaclotide might be associated with diarrhea
leading to discontinuation or dose reduction; however, this was
not very common (in one study, 4.7% discontinued the medica-
tion because of diarrhea) (68,69). The most common reasons for
discontinuation over the first year of treatment were loss of effi-
cacy and insurance coverage barriers related to obtaining pre-
scription refills and not discontinuations because of adverse
events, in a retrospective analysis at a large health system (70).
Descriptively, there were no clear differences in outcomes among
individuals older than 65 years in clinical trials, although the
sample size was too small to support formal analysis on differ-
ences in outcomes related to age.
Recommendation 9: In adults with CIC who do not respond to OTC
agents, the panel recommends the use of plecanatide over
management without plecanatide (strong recommendation,
moderate certainty of evidence).
Implementation considerations
·· Can be used as a replacement or as an adjunct to OTC agents
Duration of treatment in trials was 12 weeks, but the drug label
·
does not provide a limit.
May be associated with side effects of diarrhea leading to
discontinuation of treatment
Plecanatide
Summary of evidence. Three 12-week randomized double-
blinded placebo-controlled trials evaluated the use of plecanatide
for the management of CIC (71–73). The studied dose of pleca-
natide was 3 mg/6 mg daily, and all studies were conducted in the
United States and Canada. Plecanatide is a guanylate cyclase-C
agonist, which increases cyclic guanosine monophosphate con-
centrations resulting in luminal chloride and bicarbonate secretion,
thereby increasing intestinal fluid and accelerating GI transit.
Benefits and harms. The pooled data showed that the use of
plecanatide in adults with CIC leads to an increase in the number
of CSBMs per week (MD 1.1, 95% CI 0.85–1.35) and SBMs per
week (MD 1.66, 95% CI 1.37–1.94) and improves the quality-of-
life scores. The intervention group had increased responder rates,
© 2023 by The American College of Gastroenterology and the American Gastroenterological Association
Clinical Practice Guidelines 15
defined as $3 CSBMs per week and $1 CBSM over baseline for
$9 of 12 weeks including $3 of the last 4 weeks, compared with
placebo (RR 1.78, 95% CI 1.46–2.18), 88 more per 1,000 (from 52
to 134 more). Participants treated with plecanatide might have
higher rates of reported diarrhea leading to treatment discon-
tinuation (RR 5.39, 95% CI 2.40–12.11), 27 more per 1,000 (from
9 to 69 more). The use of plecanatide might improve stool con-
sistency based on the Bristol Stool Form Scale compared with
placebo (MD 0.83, 95% CI 0.6–1.05).
Certainty in evidence of effects. The certainty of evidence was
high for outcomes of CSBM and SBM frequency and QOL and
moderate for diarrhea, leading to treatment discontinuation, se-
rious adverse events, and stool form. The panel rated down cer-
tainty of these outcomes because of imprecision. The overall
certainty in evidence for plecanatide was moderate.
Discussion
Plecanatide is a pH-dependent guanylate cyclase-C agonist
approved by the FDA for CIC at a dose of 3 mg daily taken with
or without food. Plecanatide is also approved at the same dose
for IBS-C. Plecanatide may have beneficial concurrent effects
with relief in abdominal pain based on indirect evidence from
IBS-C trials (74). Individuals using plecanatide might be at
higher risk of diarrhea leading to discontinuation of medica-
tion; however, the absolute risk seems small (68). Descriptively,
there were no clear differences in outcomes among individuals
older than 65 years in clinical trials, although the sample size
was too small to support formal analysis on differences in
outcomes related to age.
5-HT4 AGONIST
Recommendation 10: In adults with CIC who do not respond to OTC
agents, the panel recommends the use of prucalopride over
management without prucalopride (strong recommendation,
moderate certainty of evidence).
Implementation considerations
· Duration of treatment in trials was 4–24 weeks, but the drug label
does not provide a limit.
·· Can be used as a replacement or as an adjunct to OTC agents
May be associated with side effects of headache, abdominal
pain, nausea, and diarrhea
Prucalopride
Summary of evidence. Five 12-week randomized double-blinded
placebo-controlled trials evaluated the use of prucalopride (2 mg
daily) for the management of CIC (75–79). The studies were
conducted in the United States, Europe, and the Asia-Pacific re-
gion. The 4 mg dose has also been studied (75). Prucalopride is a
selective, high-affinity 5-HT4 agonist that promotes neurotrans-
mission by the enteric neurons resulting in stimulation of the
peristaltic reflex, intestinal secretions, and GI motility.
Benefits and harms. Compared with placebo, prucalopride
resulted in an increased number of CSBMs per week (MD 0.96,
95% CI 0.64–1.29). SBMs per week was not studied in any of the
included study. Responder rates, defined as $3 CSBMs per week,
were higher in the prucalopride group (RR 2.37, 95% CI
The American Journal of GASTROENTEROLOGY
 16 Chang et al
1.97–2.85) with 165 more responders per 1,000 (range 117–222
more). An alternative responder end point, deemed alternative
end point A, defined as $3 CSBM per week and $1 CBSM over
baseline for $75% of study weeks, was higher in the prucalopride
group (RR 2.51, 95% CI 1.97–3.21) with 109 more responders per
1,000 (range 70–160 more). The rates of diarrhea leading to
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treatment discontinuation might be higher in the prucalopride
group compared with placebo (RR 3.00, 95% CI 1.89–4.78). The
occurrence of serious adverse events was low; however, the CI
around the summary estimate was imprecise and included a
possible increased risk. PAC-QOL, where lower scores are better,
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improved in 4 studies in the prucalopride group compared with
placebo (MD 0.32 lower, 95% CI 0.41–0.23 lower). Definitions
and scales used to assess stool form varied widely across
studies and could not be pooled. Global relief was reported in 4
studies and defined as those who felt that treatment was extremely
or quite a bit effective, and the responder rates were higher in the
prucalopride group compared with placebo (RR 2.09, 95% CI
0.15–3.0).
Certainty in evidence of effects. We rated the certainty of evi-
dence as high for outcomes of CSBM frequency, responder rate,
and alternative end point A and moderate for diarrhea, leading to
treatment discontinuation, serious adverse events, quality of life,
and global relief (because of small event rates and wide CIs
around the summary estimates). The overall certainty in evidence
for prucalopride was moderate.
Discussion
For prucalopride, a selective agonist of serotonin 5-HT4 recep-
tors, the recommended dose is 2 mg once daily in adults and 1 mg
daily in individuals with severe renal impairment (i.e., creatinine
clearance ,30 mL/min) (80). The efficacy in persons 65 years and
older is comparable with the overall study population. Besides
increasing bowel frequency, prucalopride also improved con-
stipation symptoms, abdominal symptoms, quality of life, and
satisfaction with treatment vs placebo assessed with the PAC
instrument (81). Arguably, these effects are at least partly
explained by the ability of prucalopride to induce and increase the
amplitude of colonic high-amplitude propagated contractions
(73,82). Such high-amplitude propagated contractions propagate
colonic contents (83).
The most frequent, generally transient, side effects are
headache, abdominal pain, nausea, and diarrhea (84). In most of
the individuals who reported headache and diarrhea, this side
effect occurred within the first week of treatment and typically
resolved within a few days. Five percent of individuals dis-
continued prucalopride because of side effects. Cardiovascular
adverse events were not more common than placebo. In a safety
database of 4,476 subjects, 4 individuals attempted suicides and
2 completed suicides, both of whom had discontinued pruca-
lopride more than 1 month before the event. The label cautions
patients and clinicians to be alert to unusual changes in mood
and behavior and suicidal ideation. It is, however, unclear what
the mechanism of action is or whether there is a causal associ-
ation between the use of prucalopride and risk of suicide (85).
No drug-associated risks of miscarriage, major birth defects, or
adverse maternal or fetal outcomes have been identified. Pru-
calopride is contraindicated in patients with intestinal perfo-
ration or obstruction, Crohn’s disease, ulcerative colitis, and
toxic megacolon/megarectum.
The American Journal of GASTROENTEROLOGY
LIMITATIONS AND EVIDENCE GAP
An important limitation of this body of evidence was that clinical
trials did not uniformly evaluate interventions for patient im-
portant outcomes on efficacy, adverse effects, and tolerability.
Importantly, there was a paucity of data for the most commonly
used treatments of CIC such as fiber, lactulose, senna, and doc-
usate. There was also variability in the definition of inclusion
criteria, efficacy, and tolerability outcomes, as well as variance in
acceptable clinical trial length by regulators over time. Most of the
included studies followed the patients for the short term, and the
safety and tolerance of these medications in the long term is not
well studied. Future research is needed to assess the long-term
safety of these medications and to assess whether the patients
develop tolerance to these medications over time. In our sys-
tematic review, we compared individual drugs against placebo
arms and did not aim to inform the relative efficacy of phar-
macological agents. Network meta-analysis is an appropriate
statistical method to facilitate indirect comparison against a
common comparator such as placebo or other active treatment
(8). However, for the reasons stated, readers should be cau-
tioned on the limitation of indirect comparisons to support
substantive claims on superiority or inferiority to inform care or
policy decisions.
This guideline is limited to covering pharmacological inter-
ventions for the treatment of CIC in otherwise healthy adults and
does not apply to pediatric populations or to individuals who are
pregnant or with opioid-induced constipation or malignancy.
The evidence on the management of constipation during preg-
nancy has been reviewed in a recent publication that discusses the
safety of almost all the pharmacological agents assessed in this
guideline (86). This guideline does not review anorectal evacua-
tion disorders that were evaluated in a recent ACG guideline (87)
and an AGA review (80). We also did not assess the efficacy of
dietary fiber including fruit-based laxatives in CIC, which was
evaluated in a recent systematic review (8). Other interventions
not included in this review include lifestyle modifications, such as
increasing water and physical activity, and other pharmacological
agents, such as elobixibat, mizagliflozin, naronapride, tegaserod,
tenapanor, or velusetrag, or the efficacy of surgical interventions
for the management of CIC. We did not assess the evidence on the
use of probiotics for the treatment of CIC, but it has been syn-
thesized elsewhere in a recent systematic review (88). Although
we considered the cost of pharmacological agents evaluated in
this guideline during the evidence to decision-making process, we
did not perform formal cost-effectiveness analyses and refer the
audience to recently published evidence that addresses this topic
(89). There was no patient representative in the guideline de-
velopment panel, which is a limitation for this study.
IMPLEMENTATION, COST, AND HEALTH
EQUITY CONSIDERATIONS
This document provides a comprehensive outline of the various
OTC and prescription pharmacological agents available for the
treatment of CIC. The guidelines are meant to provide a template
for approach to management and practitioners should engage in
shared decision making based on the preference of patients and
cost and availability of the medications. Although the recom-
mendations in this guideline were based on available evidence, the
implementation considerations included suggestions from the
collective experience of the expert panel and may not be based on
VOLUME 00 | MONTH 2023 www.amjgastro.com

evidence. Most of the medications assessed in this guideline
document are readily available; however, some of them are still
available only in brand name formulations because generic for-
mulations do not exist. As a result, it is important to consider the
out-of-pocket expenses for patients that may depend on pre-
scription coverage with various insurance plans (89). Prior au-
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thorization might be required for some of the medications (90).
The clinical decision support tool is available from the website
of AGA.
PLANS FOR UPDATING
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Considerable resources are expended for the development of
guidelines, and keeping guidelines up to date is a challenging
process. Future update of this guideline will depend on the
availability of new evidence on the existing interventions and new
intervention. We hope to incorporate the advances in the tech-
nological platforms and models of guideline development in the
future updates without duplication or reproduction of the current
guideline document.
ACKNOWLEDGMENT
We thank Claire Neumann, Stephanie M. Demian, Jenny Castano,
and Nelly Ahmet for their help for coordination of work for this joint
guideline.
CONFLICTS OF INTEREST
Financial support: None
Potential competing interests: L.C. has served as a member of the
scientific advisory boards for Ardelyx, Atmo, Immunic, Ironwood,
and Mauna Kea Technologies; has served as a consultant for Bausch
Health and Trellus Health and a speaker for Ironwood; has received
research support from the National Institute of Health, Arena, AnX
Robotica, Ironwood, and Vanda Pharmaceuticals; and has stock
options with ModifyHealth and Trellus Health. W.D.C. has served as
a consultant for AbbVie, Ardelyx, Biomerica, Ironwood, Isothrive,
QOL Medical, Nestle, Phathom Pharmaceuticals, Redhill, Salix/
Valeant, Takeda, and Vibrant; has received research grants from
FDA, NIH, Commonwealth Diagnostics, QOL Medical, and Salix;
has board membership at ACG, GI on Demand, International
Foundation for Functional Gastrointestinal Disorders (IFFGD), and
the Rome Foundation; holds patents for Digital Manometry and the
Rectal Expulsion Device; and has stock options in Coprata, Dieta,
Kiwi Bioscience, ISOThrive, and Modify Health. C.V.A. has served as
a consultant for Owlstone Medical; and has stock options in My Total
Health and Owlstone Medical. A.E.B. receives royalties from a patent
created for Medispira Medical Technologies. L.A.H. has consulted
for AbbVie/Ironwood, Alyman, and Takeda. E.D.S has served as a
consultant for Salix, Mahana, Ardelyx, Takeda, GI Supply and
Neuraxis outside the scope of the current work. He holds a patent on
the Rectal Expulsion Device. A.J.L. has consulted for Vibrant and
Mylan; owns equity in Johnson & Johnson and Bristol Meier &
Squibb; and has received research support from Takeda, Vanda,
Shire, and Biomerica. The other authors have no financial conflicts to
disclose.
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